Hemochromatosis is an iron overload disorder. The affected individual stockpiles iron in the body to the extent that it accumulates to an undesirable amount at various locations, causing harm to the normal functioning of the tissue in which it is stored.
Types of Hemochromatosis and Causes
The main causes which result in hemochromatosis are as mentioned below:
- A defective genetic make-up, which results in increased iron absorption via the gastrointestinal tract and the excess iron accumulates in the organs such as the heart. This type of hemochromatosis usually remains undiagnosed until the symptoms appear.
- An excess iron accumulation post blood transfusions in blood-related disorders such as anemia and thalassemia. Prolonged alcohol consumption may also contribute to hemochromatosis
Both primary and secondary hemochromatosis has been reported, the former being far more common. Primary or hereditary hemochromatosis exists in several forms, of which Type 1 is the most common. The organs in which iron is usually stored include the heart, the liver, the skin, the pancreas, and the joints. The human metabolism is that iron excretion is more or less stable regardless of intake and absorption. As a result, excessive iron cannot be expelled through a natural course, when it is significantly increased in hemochromatosis. This leads to progressive and often irreversible damage to the tissues, which results due to iron overload, and could become fatal, unless the condition is treated well in time.
Genetic Basis – Hereditary Hemochromatosis
Hereditary Type 1 hemochromatosis is among the commonest of genetic diseases found in the USA and is especially prominent among individuals of North European descent.It is caused by mutations in the HFE gene, the ones being found most often includes C282Y and H63D. However, hemochromatosis as a whole is due to mutations in one of several genes, the more frequently found ones being HAMP, HFE, HJV, SLCO40A1, and TFR2 genes. Type 2 hemochromatosis is the result of the abnormality in the HJV or the HAMP genes, while the TFR2 gene mutation causes Type 3. Abnormality of the SLC40A1 gene is the reason for Type 4.
All these genes are alike in coding for proteins which regulate iron absorption, transport, and storage in the body. When they are abnormal, excessive absorption, overriding regulatory mechanisms in the gut wall can lead to high levels of iron in the serum and altered patterns of iron storage in the body’s tissues, with toxic effects on their functions. One of these proteins is the liver hormone called hepcidin, which cannot function normally in hemochromatosis
Inheritance of Hereditary Hemochromatosis
The inheritance of the genes responsible for Types 1, 2 and 3 are autosomal recessive, and therefore each parent must pass on one abnormal copy of the gene before the child is clinically affected. The parents are typically carriers with one mutated copy of the gene each, and with no features of the condition. Type 4 is inherited in an autosomal dominant fashion and so if one abnormal gene copy is transmitted to the offspring will have the disease. This type is usually seen in offspring of parents are also affected. Overall, however, not more than one in ten individuals with two copies of the gene mutation actually show significant signs and symptoms of hemochromatosis.
Forms of Hemochromatosis
In keeping with the genetics and the time of onset, there are different clinical forms of hemochromatosis, such as:
- Juvenile hemochromatosis is observed in young people between 15 and 30 years, due to mutations in the hepcidin or hemojuvelin genes
- Neonatal hemochromatosis which is due to autoimmune liver deposition of iron in intrauterine life
- Secondary hemochromatosis which is due to excessive breakdown of red cells and treatment by many repeated transfusions, leading to the accumulation of iron from these red cells in the body. Chronic liver disease, renal dialysis, sideroblastic anemia, thalassemia, are all examples of conditions in which this may occur. Another cause could be atransferrinemia, aceruloplasminemia, which refers to the lack of transport proteins in the serum leading to iron buildup in the blood. Chronic hepatitis C, alcoholic liver disease or fatty degeneration of the liver are liver conditions which may cause secondary hemochromatosis. Some individuals may, rarely, develop secondary hemochromatosis because of excessive consumption of iron pills with or without the intake of vitamin C, (Iron absorption increases in the presence of Vitamin C), injections of iron or blood transfusions.